Variant 7-2652204-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000258796.12(TTYH3):c.889C>G(p.Leu297Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,613,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

TTYH3
ENST00000258796.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

Variant links:

Genes affected

TTYH3 (HGNC:22222): (tweety family member 3) This gene encodes a member of the tweety family of proteins. Members of this family function as chloride anion channels. The encoded protein functions as a calcium(2+)-activated large conductance chloride(-) channel. [provided by RefSeq, Jul 2008]

TTYH3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15349776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTYH3	NM_025250.3 linkuse as main transcript	c.889C>G	p.Leu297Val	missense_variant	8/14	ENST00000258796.12	NP_079526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTYH3	ENST00000258796.12 linkuse as main transcript	c.889C>G	p.Leu297Val	missense_variant	8/14	1	NM_025250.3	ENSP00000258796	P3	Q9C0H2-1
TTYH3	ENST00000429448.2 linkuse as main transcript	c.889C>G	p.Leu297Val	missense_variant	8/15	2		ENSP00000413757	A1	Q9C0H2-4
TTYH3	ENST00000407643.5 linkuse as main transcript	c.793C>G	p.Leu265Val	missense_variant	7/13	5		ENSP00000385316		Q9C0H2-2
TTYH3	ENST00000403167.5 linkuse as main transcript	c.376C>G	p.Leu126Val	missense_variant	4/10	5		ENSP00000385015		Q9C0H2-3

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000108

AC:

AN:

249864

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000195

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000240

AC:

351

AN:

1460968

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

169

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000295

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000184

AC:

AN:

152386

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000313

Hom.:

Bravo

AF:

0.000121

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 01, 2023

The c.889C>G (p.L297V) alteration is located in exon 8 (coding exon 8) of the TTYH3 gene. This alteration results from a C to G substitution at nucleotide position 889, causing the leucine (L) at amino acid position 297 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.38

T;.;.

Eigen

Benign

-0.098

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

M;.;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.013

D;D;T

Sift4G

Uncertain

0.045

D;D;D

Polyphen

0.067

B;.;P

Vest4

0.36

MVP

0.093

MPC

0.68

ClinPred

0.17

GERP RS

2.2

Varity_R

0.17

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over